Insulin-like growth factor-1 prevents Aβ[25-35]/(H2O2)-induced apoptosis in lymphocytes by reciprocal NF-κB activation and p53 inhibition via PI3K-dependent pathway

The role of insulin-like growth factor (IGF-1) as neural survival factor for the treatment of Alzheimer's disease has recently gained attention. The present study shows that IGF-1 protects lymphocytes from (10, 30 mu M) A beta[(25-35)] and (25, 50, 100 mu M) H2O2-induced apoptosis through NF-kappa B activation and p53 down regulation involving the phosphoinositide 3-kinase (PI-3K)-dependent pathway as demonstrated by using either (25 mu M) LY294002 (PI-3K inhibitor), (10 nM) ammonium pyrrolidinedithiocarbamate (PDTC; NF-kappa B inhibitor), 50 nM pifithrin-alpha (PFT; p53 inhibitor) or by using immunocytochemistry detection of NF-kappa B and p53 transcription factors activation. Importantly, IGF-1, PDTC and PFT were able to protect and rescue lymphocytes pre-exposed to 10 mu M A beta[(25-35)], even when the three compounds were added up-to 12 h post- A beta[(25-35)] exposure. Altogether these results suggest that survival/rescue of lymphocytes from A beta[(25-35)] toxicity is determined by p53 inactivation via IGF-1/PI-3K pathway.